Visualizing beta cells in morbid obese patients with T2D before and after bariatric surgery

In order to evaluate the difference in beta cell mass in morbid obese patients
with type 2 diabetes mellitus (T2D) before and after Roux-en-Y gastric bypass
(RYGB) we aim to compare quantitative PET imaging of the pancreas in this
patient group before and after surgery. We propose to measure the uptake of
68Ga-NODAGA-exendin-4 in the pancreatic beta cells of these patients.
Furthermore, we aim to compare uptake of the radiolabeled tracer to beta cell
function measured by laboratory parameters. These highly relevant data will
provide us with more information on the contribution of the beta cells to the
mechanisms behind resolution of T2D after bariatric surgery and on the
prognostic value of pre-operative beta cell mass to T2D resolution. This might
be of great interest for the assessment of RYGB as an alternative therapy in
patients with T2D and a BMI <35, who currently do not meet the international
guidelines for bariatric surgery.

The main objective is to examine the change in 68Ga-exendin tracer accumulation
in the pancreas (i.e. beta cell mass) after RYGB by quantitative analysis of
PET images before and one year after RYGB in morbid obese patients with type 2
diabetes.

Patients will be recruited at the Rijnstate hospital in Arnhem. We aim to
include 12 patients in this study. After recruitment of the participating
individuals, all patients will undergo an enrollment check at Rijnstate
hospital consisting of a medical interview, a physical examination performed by
a qualified physician and recent blood samples for standard laboratory checks
(blood counts, electrolytes, liver enzymes, creatinine, inflammation
parameters) will be analyzed. Then, the participating individuals will undergo
an oral glucose tolerance test (OGTT) and a glucose-dependent
arginine-stimulation test at the Rijnstate hospital. The 68Ga-NODAGA-exendin-4
PET/CT is performed at the Radboudumc one hour after the administration of 100
MBq 68Ga-NODAGA-exendin-4. The OGTT/arginine test and the PET/CT will be
performed before RYGB and approximately one year after RYGB.

All individuals will undergo physical examination and blood sampling for
standard laboratory parameters in the Rijnstate hosptital. In addition, all
patients will undergo an oral glucose tolerance and an arginine stimulation
test. In the Radboudumc, 68Ga-NODAGA-exendin-4 will be administered
intravenously and scanning will be performed one hour after injection of the
tracer. After injection of the radiopharmaceutical, blood samples will be drawn
from an intravenous catheter for determination of blood glucose levels. Also,
blood pressure will be measured. Injection of the radiopharmaceutical may
theoretically result in nausea and headache as has been reported for (much
higher doses) of Byetta® in therapy studies. In addition, single cases of low
blood pressure and low blood glucose levels have been described. Although low
blood glucose levels only occurred after accidental heavy overdosing of
Byetta®, patients will be closely monitored. However, in a previous study
(CPOP-EX), we did not observe any side or adverse effects after
111In-DTPA-[K40]-exendin-4 injection for all 20 patients included.
The expected radiation exposure will be 5 mSv per PET/CT scan and 10 mSv for
both PET/CT scans. The scans are performed over approximately 1.5 years. The
radiation exposure over this period is considered minimal to little. However,
if the technique would indeed allow sensitive and specific visualization and
quantification of beta cell mass in patients after RYGB, the impact on
evaluation of bariatric surgery as an alternative therapy for T2DM would be
very high.